The studies described in this supplemental application are designed to explore the poorly understood areas of bile secretion and cholestasis. Detailed quantitative functional and structural studies will be carried out in the laboratory rat, in collaboration with Dr. Albert L. Jones. Correlations will be drawn between liver function, as reflected in bile acid and lipid secretion and tissue and serum bile acid and lipid concentrations, and the ultrastructure of the hepatocyte determined employing quantitative morphometric techniques. The studies will provide the first such quantitative and correlative data on structure and function which relate both to the process of bile secretion and to the abnormalities of liver structure and function that are observed in cholestasis. They are expected to clarify the mechanism of bile secretion and the pathophysiology of the syndrome of cholestasis.